Cartilage is a unique tissue that consists of extensive extracellular matrix whose function is to absorb shock in the joint. Genetic defects of cartilage proteins are responsible for certain types of osteoarthritis. Abnormal expression and degradation of cartilage components also lead to impaired function of joints. The purpose of this project is to understand the molecular mechanisms underlying cartilage formation in normal development and to identify factors involved in the differentiation of chondrocytes. Several major cartilage components have been cloned and their primary structures have been determined. The structure and function of these proteins have been studied using both synthetic peptides and recombinant proteins produced in bacteria and mammalian cells. Sequences regulating transcription of the collagen II gene have been identified in the promoter and the enhancer region. These sequences have been shown to interact with multiple nuclear factors. Several protein factors which bind to the enhancer have been cloned and characterized. The function of these factors is being tested by DNA transfection. Glucocorticoid responsive sequences have been identified in the promoter and the first intron of the link protein gene. Without these sequences, the promoter activity of the link protein gene is significantly reduced in chondrocytes. Retinoic acid decreases the expression of the link protein gene. The region with which retinoic acid interacts to produce this effect has been localized within the first intron of the link protein gene.